IL-2 reverses the inhibition of cytotoxic T-cell responses induced by 5-(3,3' dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) in vitro.
One of the major limitations in the use of triazene compounds for inducing increased immunogenicity of tumor cells in vivo (i.e. chemical xenogenization) is the profound immunodepressive activity of these drugs. The present study analysed the inhibitory effects of DTIC on various T-dependent immune responses in mice in an attempt to determine the mechanism of action and appropriate treatments for reverting the immune damage produced by the agent. Results obtained show that treatment with DTIC in vivo produced: (a) inhibition of spleen cell proliferation; (b) reduced IL-2 production in response to allogeneic stimuli; (c) reduction of the generation of IL-2R + CD8 + cells in allogeneic MLC; (d) inhibition of allo-CTL generation. The addition of IL-2 to MLC on day 2 of the co-culture restored full allogeneic CTL responses. These data suggest that exogenous IL-2 could be used to counteract DTIC-induced depression of T-cell reactivity, which is presumably involved in hosts' responses against autochthonous xenogenized tumor cells.
Tentori
L
L
Institute of Experimental Medicine, C.N.R., Rome, Italy.
Leonetti
C
C
Lanzilli
G
G
Bonmassar
E
E
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003606:Dacarbazine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003606:Dacarbazine